rs3215202

chr4-46992955-GAA-Gchr4-46992955-GAA-GAchr4-46992955-GAA-GAAAchr4-46992955-GAA-GAAAAchr4-46992955-GAA-GAAAAAchr4-46992955-GAA-GAAAAAAchr4-46992955-GAA-GAAAAAAAAchr4-46992955-GAA-GAAAAAAAAAchr4-46992955-GAA-GAAAAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000809.4(GABRA4):c.87-11_87-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,299,454 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: GABRA4 NM_000809.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167

Genes affected

GABRA4 (HGNC:4078): (gamma-aminobutyric acid type A receptor subunit alpha4) Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. This gene encodes subunit alpha-4, which is involved in the etiology of autism and eventually increases autism risk through interaction with another subunit, gamma-aminobutyric acid receptor beta-1 (GABRB1). Alternatively spliced transcript variants encoding different isoforms have been found in this gene.[provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA4	NM_000809.4	c.87-11_87-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000264318.4
GABRA4	NM_001204266.2	c.30-11_30-10del		splice_polypyrimidine_tract_variant, intron_variant
GABRA4	NM_001204267.2	c.30-11_30-10del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA4	ENST00000264318.4	c.87-11_87-10del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000809.4	P1

Frequencies

GnomAD3 genomes AF: 0.000146 AC: 21 AN: 144084 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000486

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000687

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000223

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000228 AC: 263 AN: 1155314 Hom.: 0 AF XY: 0.000212 AC XY: 124 AN XY: 584308

Gnomad4 AFR exome AF: 0.000716

Gnomad4 AMR exome AF: 0.000136

Gnomad4 ASJ exome AF: 0.0000443

Gnomad4 EAS exome AF: 0.0000835

Gnomad4 SAS exome AF: 0.000323

Gnomad4 FIN exome AF: 0.0000850

Gnomad4 NFE exome AF: 0.000223

Gnomad4 OTH exome AF: 0.000325

GnomAD4 genome AF: 0.000146 AC: 21 AN: 144140 Hom.: 0 Cov.: 0 AF XY: 0.0000860 AC XY: 6 AN XY: 69730

Gnomad4 AFR AF: 0.000485

Gnomad4 AMR AF: 0.0000686

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000224

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00103 Hom.: 91

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3215202; hg19: chr4-46994972;